
Chapter 10: Research into Receptors, Pathways, Cross-Talk and the Utility of Existing Drugs
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Description
Dr. Hung begins this chapter by explaining the structure of receptors and how explosion of knowledge about signal transduction set the stage for targeted therapy.
He talks about his work on tyrosine kinase and interventions in signaling cross talk, explaining this concept. Throughout this chapter, Dr. Hung explains that he focuses on investigations into how existing drugs can intervene in molecular and genetic processes, as this avoids time-intensive drug research.
Next Dr. Hung talks about trials involving the HER2 gene and head and neck and colon cancers. He explains that his work on kinases addresses the needs of the twenty percent of breast cancer patients who are “triple negative” and whom clinicians simply don’t know how to help.
“There are twenty thousand proteins in a cell,” Dr. Hung says. “But we only need fifty” to make a difference to cancer patients. He explains the “huge paradigm shift” that has occurred and talks about the future of research on cancer, breast cancer, and pancreatic cancer.
Identifier
HumgMC_02_20140307_C10
Publication Date
3-7-2014
City
Houston, Texas
Interview Session
Topics Covered
The Interview Subject's Story - The Researcher; The Researcher; Overview; Definitions, Explanations, Translations; Discovery and Success; Professional Path; On Research and Researchers; Understanding Cancer, the History of Science, Cancer Research; Formative Experiences; Discovery, Creativity and Innovation; Healing, Hope, and the Promise of Research
Transcript
T.A. Rosolowski, PhD:
Yeah. Well, would you like to go back to your research story at this point?
Mien-Chie Hung, PhD:
Okay.
T.A. Rosolowski, PhD:
So we --- you were kind of going through a lot of stuff. You were talking --- you were talking about …
Mien-Chie Hung, PhD:
We talked about translation, right?
T.A. Rosolowski, PhD:
We did. We talked about translation.
Mien-Chie Hung, PhD:
Okay. So why not let me share with you some --- we talked about HER2/neu, talked about doing gene therapy, and then I moved to clinical trial. And now I’m developing a VISA vector and targeting other cancer types ….
T.A. Rosolowski, PhD:
Right.
Mien-Chie Hung, PhD:
…right? So that’s one arm that … because gene therapy and that --- you know how I come with gene therapy, but through this kind of journal club, through the environment of MD Anderson. Now, as I told you, for me to discover a project, it’s not a difficult time ….
T.A. Rosolowski, PhD:
Right.
Mien-Chie Hung, PhD:
… it’s easy now. And then we can pick up … at this moment, this is the most important project. This most important project may not be most important 10 years from now, but 10 years from now …
T.A. Rosolowski, PhD:
Right ___ yeah.
Mien-Chie Hung, PhD:
… already ___ . Why not, for example.
T.A. Rosolowski, PhD:
But also --- excuse me just a minute. But --- I mean, there --- there’s something exciting about this sense of immediacy. You know, like, bang! Here it is, right now. This is what we need to do and you’re ready to move on it.
Mien-Chie Hung, PhD:
Yes.
T.A. Rosolowski, PhD:
You know, you know.
Mien-Chie Hung, PhD:
And --- the --- my expertise --- HER2/neu is a receptor. You know receptor, right? Okay. So there’s a circle signal transaction.
T.A. Rosolowski, PhD:
But, why don’t you explain for the --- what --- talk to me about a receptor. What does that mean?
Mien-Chie Hung, PhD:
Receptors include HER2/neu, include the EGF receptor. There were a molecule originally been discovered. So they are in the cell surface. They --- they --- they are integral membrane for the --- this is the cell surface and there’s a membrane here. But the receptor crosses that line. So one half is outside of the cell, the other inside the cell. And their function has traditionally been thought to be --- to be able to communicate outside of the cell, inside the cell. For example, you have something coming. You want to tran --- transduce some stress, some signal to the cell. You let it go to these receptors and then the ____, there’s a portion outside called extracellular, right? But then after you have something stimulate this extracellular site, you make it pass the measure message to the intracellular site. And this intracellular portion induce whatever signal. And that’s what we call signal pathway. And then you can employ the cell to say, this signal comes in, it makes the cell say, hey, my friend, now you had to grow now from 1 to become 2; 2 become 4, right? So for example, why do you develop a tumor? You develop tumor in --- in a very simple term, say, you’re not supposed to grow, stop now. But it keeps on growing into a tumor, right? So it keeps on growing --- an abnormal growing. And because that’s not the only --- the only type of cancer is a tumor, to say. And --- but those signal from 1 to 2 , 2 to 4, you have to pass signal from cell surface. Something’s stimulated from outside, then transfers the signal to the nucleus, right? So cell in the nuc --- and the nucleus ___ the DNA double helix, it starts to replicate… and it starts: 1 becomes 2, 2 to 4. All this signaling from outside to the inside, it’s called signal transduction. It’s more --- it’s like you run the 400 meter with a four-person race. Right? So I pass and run the first one. You’re the second one, so I pass it to you, right? Then you pass to the third one, then you pass four. Then you compete ____. That’s whole cycle. You --- you know what I’m saying?
T.A. Rosolowski, PhD:
I do, yes.
Mien-Chie Hung, PhD:
A race, and they have to call a ….
T.A. Rosolowski, PhD:
Relay race.
Mien-Chie Hung, PhD:
Relay … relay … yeah, relay. Okay.
T.A. Rosolowski, PhD:
Yeah.
Mien-Chie Hung, PhD:
So signal transduction is like that. And signal transduction in molecular cell biology, it started maybe --- started from mid ‘80. Started from mid ‘80. And then, people don’t know much about it. Or could have been even earlier --- early in ’80. But now, we should know so much about a cell, how the signal transduces. And then many, many --and this signal pathway, because these signal pathways are very critical to control cell growth --- cancer cell growth. Well, why does cancer cell become an abnormal growing cell? Why does a cancer cell metastasize from primary tumor, and go on to –their, their properties change. Of course, not only their properties change, their environment may be changing rapidly. But first, their property --- this guy has to be changed, right?
T.A. Rosolowski, PhD:
Right.
Mien-Chie Hung, PhD:
And the change --- they all change their signal. So now, in the last 20, 30 years, we know so much about signaling now. And all the signaling now has provide for targeted therapy. HER2/neu, EGF receptor. These are early stages for developing target therapy, but now there are tons of examples, like ___ 0:57:55 now is a target for melanoma. They --- there are other examples out there. There are a lot of examples. But then when people understood this is a signal pathway, originally, it was HER2 overexpression, right? And so if there is HER2 overexpression, now we block it. But HER2 always actually produces a signal, right? You can block the signal, too. And all of them are potential _____
T.A. Rosolowski, PhD:
At various stages.
Mien-Chie Hung, PhD:
And that’s where the tyrosine kinase inhibitor comes in. Tyrosine kinase is an enzyme. These receptors --HER2/neu is not only a cell surface receptor, they are also kinases, and this kinase is a enzyme. But if you develop inhibitor, then this ____ 0:58:32. So with this kind of a circular signal transduction being known --and this particular department call Molecular Cellular Oncology, right? We focus on cancer molecular cell biology ___, we do a lot of signaling. And the nice thing is, when you know the signal, this signal allows you to --- to understand why this cell metastasizes. Why this cell is a cancer cell and not a normal cell. So in that situation, we can understand what signal pathway was screwed up to make it become cancer. And then, if you can fix that, then that potential will drop. Similar to HER2 overexpression. But HER2 overexpression, is just one of the early examples. And --- and when a lot of people develop this kind of inhibitor, you block the signal pathways. There are many, many, many drafts, you know, approved by FDA and they are all ongoing right now. However, cancer is very smart. A cancer cell, when you block it, it cannot grow. They die, right? But out of one million cancer cell, they want to survive too, right? They start mutating. They also make it so that they become resistant. That’s why --- other reasons why --- remember cancer patient after treatment, five years later, they recur. Right? In some of them it is because of the cell which was originally there, and they just start to develop. But in many --- in some occasions, it’s because especially in human ___ 0:59:58 cancer. And several cancer type is already --- we you do target therapy. Okay, this particular cancer, HER2/neu overexpression, you can use a receptor or use a drug, too. But after treatment, some of the patients respond, they are cured, but some of the patients, before they complete cure, their cancer recurs. You know why? They become a mutation, and that drug os no longer useful. So then we …
T.A. Rosolowski, PhD:
How quickly does that happen?
Mien-Chie Hung, PhD:
From case to case, it’s different, okay? But in a case of recent --- I may know more in a few months.
T.A. Rosolowski, PhD:
So very fast.
Mien-Chie Hung, PhD:
Yeah. Then --- then they already are strengthen. Those who can be cured, they cure. But if we don’t completely cure, then before the cure, some of them mutate in such a way that they become --- the drug no longer useful, right? They --- they don’t care what drug. They start to develop, right. And so now, we --- the knowledge that we have with this signal transduction, we can --- I should not say easily, but it’s not difficult at all to identify the so-called signal cross talk.
T.A. Rosolowski, PhD:
Cross talk.
Mien-Chie Hung, PhD:
Yeah.
T.A. Rosolowski, PhD:
Okay.
Mien-Chie Hung, PhD:
For example, you take this drug to treat it, and if this cancer cell, it’s been blocked, then the center of the particular pathway is actively blocking it. But then, you identify there’s a signal pathway cross talking with this one . And then when you block this one, we cannot really block it. Let me draw that for you. One specific example. So, this is the pathway and this cause cancer. Okay? So people develop an inhibitor here.
T.A. Rosolowski, PhD:
Okay. So you’re intervening in one place.
Mien-Chie Hung, PhD:
Yeah. But now, we found this --- this guy which causes cancer is …
T.A. Rosolowski, PhD:
Is coming from another signaling pathway.
Mien-Chie Hung, PhD:
Yeah.
T.A. Rosolowski, PhD:
Yeah. So you have to …
Mien-Chie Hung, PhD:
And so …
T.A. Rosolowski, PhD:
… attempt to intervene in another place.
Mien-Chie Hung, PhD:
… this … yeah. Yeah, you’re right. Okay, so…
T.A. Rosolowski, PhD:
Yeah. Got ya.
Mien-Chie Hung, PhD:
… then we disco ---- so for us to start here, we can study this cross talk …
T.A. Rosolowski, PhD:
Right.
Mien-Chie Hung, PhD:
We --- we can predict it before they become resistant.
T.A. Rosolowski, PhD:
Gotcha.
Mien-Chie Hung, PhD:
Or --- or after they are resistant. So now, if I have resistant cell, it’s been treated, right? And then --- they are resistant. We check these cancer cells, right? We can --- can looking for what happened. And we do a lot of this kind of stuff. And the nice thing is, if it’s an anti-cancer drug to treat the patient and they are already very resistant, then we should try to find out this one so we can then identify another pathway where we can block it, right? So that’s important. But we can even, before they do that, now every time --- if I develop new drug, before it goes to the patient, we can, in the lab, we can treat the cell to cure them. But some of them eventually develop resistance, right? So that’s going to mimic human. And so we can understand this one and identify …
T.A. Rosolowski, PhD:
And begin to ___ where those points in cross talk are.
Mien-Chie Hung, PhD:
Yeah. And then ideally say, now, they are so many drugs available.
T.A. Rosolowski, PhD:
Right.
Mien-Chie Hung, PhD:
Many of these so-called signal pathways are important. You may not even have to develop drug, because to develop a drug takes 10, 20 years. This drug A is the one you study. Then after you cross identified, the drug B --- may already --- is another drug already available. So, it is low hanging fruit. You could not do that 20 years ago, but now you can because there are a lot of drugs there already. You don’t need to really develop a drug. There were drugs 20 years. But you can take the existing drug, if they cross talk …
T.A. Rosolowski, PhD:
Right.
Mien-Chie Hung, PhD:
… then we can ___ benefit patients right away.
T.A. Rosolowski, PhD:
So it’s getting a deeper understanding …
Mien-Chie Hung, PhD:
Yeah.
T.A. Rosolowski, PhD:
… of all of the little pathways and figuring out how the existing drugs …
Mien-Chie Hung, PhD:
And that’s why this ….
T.A. Rosolowski, PhD:
….can be used to intervene.
Mien-Chie Hung, PhD:
… that’s what this department is doing.
T.A. Rosolowski, PhD:
Right, uhuh. Got you.
Mien-Chie Hung, PhD:
That’s why we are called Molecular Cell Oncology.
T.A. Rosolowski, PhD:
Yeah, yeah.
Mien-Chie Hung, PhD:
And we do a lot of this concept. And for us to identify this, it’s not piece of cake, but it’s not that difficult. Because the technology has improved. So at the very beginning for HER2, it was one big event and only HER2/neu. But why now? If this signal pathway, if this is a single cell, from outside stimulant going to single cell. Now, in the literature, there probably 200, 300 ---- 300 pathways. And several major pathways are known to be involved in specific cancer. And so we are doing a lot of this cancer. I can share with you one of the --- one of the recent examples.
T.A. Rosolowski, PhD:
Please do that.
Mien-Chie Hung, PhD:
It’s called --- it’s a skin cancer called basal cell carcinoma. It’s type of cancer cell --- a skin cancer. And then Genetics 1:04:36.3 developed a drug and they path --- by the way, a lot of these pathways are very interesting, okay, --- fundamental science. Their name come from drosophila.
T.A. Rosolowski, PhD:
Yeah?
Mien-Chie Hung, PhD:
There was two crazy scientist group who received the Nobel Prize. They took drosophila, you know, fruit fly ….
T.A. Rosolowski, PhD:
The fruit fly, yeah.
Mien-Chie Hung, PhD:
… and mutated it. ___. And after mutation, they spent their lifetime to characterize it. And then when the mutation takes place, you know, it become two --- bithorax or antennapedia because of their heg --- their legs come off easily. So there are lot of mutants and it’s called the hedgehog, called hippo …
T.A. Rosolowski, PhD:
I was wondering where that came from.
Mien-Chie Hung, PhD:
Okay, okay.
T.A. Rosolowski, PhD:
Yeah.
Mien-Chie Hung, PhD:
All those name …
T.A. Rosolowski, PhD:
Yeah.
Mien-Chie Hung, PhD:
All those names come from drosophila studies. So, then everyone has --- has a history, hedge --- and a hedgehog is one of them. You know who --- hedgehog --- hedgehog is a mutant because when that mutant --- the --- the fly, remember the fly development? After the egg, they become larva, right? And they start moving around, right? Then they don’t mature and become a fly, right? And doing the larva --- origin in --- in --- have you seen those larvae?
T.A. Rosolowski, PhD:
Yeah, they’re creepy.
Mien-Chie Hung, PhD:
Okay, so --- so the larva
T.A. Rosolowski, PhD:
Yeah.
Mien-Chie Hung, PhD:
During the development, they have a specific pattern, okay? But the hedgehog pattern is a mutant. When you have that hedgehog mutant, they don’t have this one. They look like a spiny ball.
T.A. Rosolowski, PhD:
Oh, yeah.
Mien-Chie Hung, PhD:
This look like hedgehog.
T.A. Rosolowski, PhD:
Yes. So it’s like a ball instead of a long thing.
Mien-Chie Hung, PhD:
Yeah, yeah, so that’s why it called hedgehog.
T.A. Rosolowski, PhD:
Creepy.
Mien-Chie Hung, PhD:
Okay? So --- so, otherwise …
T.A. Rosolowski, PhD:
That’s a horror --- horror movie stuff.
Mien-Chie Hung, PhD:
So --- so, otherwise hedgehog has no meaning.
T.A. Rosolowski, PhD:
Okay, I was ….
Mien-Chie Hung, PhD:
But it’s because …
T.A. Rosolowski, PhD:
… wondering about that.
Mien-Chie Hung, PhD:
… because of historical reason.
T.A. Rosolowski, PhD:
Yeah, yeah.
Mien-Chie Hung, PhD:
Okay? Okay. So hedgehog pathway is well known --that there is this mutation in the hedgehog pathway, and that mutation causes this particular type of basal cell carcinoma. It’s a skin cancer.
T.A. Rosolowski, PhD:
Okay.
Mien-Chie Hung, PhD:
And so nowadays when people developed that – you know the mechanism, right? So right now, we know the mechanism.
T.A. Rosolowski, PhD:
Okay.
Mien-Chie Hung, PhD:
Used to be to develop a drug take a long time. You had to do Phase 1, Phase 2, Phase 3, a lot of --- but nowadays, it’s so -called target therapy, like HER2 is one of the good example at that time. You talk to HER2, right? So you only treat the patient with the HER2 overexpression. If the patient is not HER2, you don’t use this drug. So you use this drug for this patient. This one is like that. You have a mutation. And then, so they deal with --- they --- they make a inhibitor to block this particular pathway and they go to Phase 1, Phase 2. Only Phase 2 FDA approve it. The good response rate was very high. Nowadays when you do a clinical trial, you select the right patient. You know this patient is going to respond. You select the population of patients to treat. So then, your response rate is very high. So when you go to Phase 1, Phase 2 FDA approve it all, you don’t have to go to Phase 3.
T.A. Rosolowski, PhD:
Oh, wow.
Mien-Chie Hung, PhD:
Used to be, you go to Phase 3. So this one --- and then, just two, three years ago, we discovered this hedgehog pathway cross talking to another pathway. And this --- another pathway is another very well known cancer pathway called mTor.
T.A. Rosolowski, PhD:
Called?
Mien-Chie Hung, PhD:
mTor. And the nice thing is, this mTor pathway …
T.A. Rosolowski, PhD:
mTor. Oh, okay.
Mien-Chie Hung, PhD:
mTor is another pathway. And remember when I talk about a pathway, I’m not talking about only one molecule. It’s a series.
T.A. Rosolowski, PhD:
It cascades kind of
Mien-Chie Hung, PhD:
Is --- yeah, cascades.
T.A. Rosolowski, PhD:
Yeah, got you.
Mien-Chie Hung, PhD:
And this is a very normal well known cancer pathway. There are a lot of drugs available.
T.A. Rosolowski, PhD:
Oh, really?
Mien-Chie Hung, PhD:
Many, many, many drugs already in the clinical trial FDA approved in that particular pathway.
T.A. Rosolowski, PhD:
So what does this do? What does mTor do?
Mien-Chie Hung, PhD:
mTor is an enzyme, it’s a kinase --- all these are kinase. And this kinase, they induce signal 2. In many cancer cell, they were abnormally activated …
T.A. Rosolowski, PhD:
Yeah.
Mien-Chie Hung, PhD:
… so they enhance those gene expression which cause abnormal tumor growth or even enhance --- enhance, you know, migration, metas --- enhance metastasis. So anyway, they are linked to the genes which are known to trigger a cancer. And they are --- they serve as these target. So the drug is already there. That’s what I’m trying to say. Low hanging fruit.
T.A. Rosolowski, PhD:
Right.
Mien-Chie Hung, PhD:
So now --- and then for this kind of drug, when you treat with it, perfect. That particular patient population will be responding very nicely. But once the cancer cell has another pathway to cross talk, some of the patient may not respond then. And so even before they develop resistance, we already predict which one.
T.A. Rosolowski, PhD:
Interesting.
Mien-Chie Hung, PhD:
Right? And in principle, you can do mutation therapy. And the very funny thing is, this particular drug with Phase 2 being approved by FDA, right, for --- for skin cancer, for the basal cell carcinoma skin cancer. But at the same time, clinical trial in ovarian cancer, in brain tumor and pancreatic cancer, this drug doesn’t work. Now we know why.
T.A. Rosolowski, PhD:
And you were able to --- now you’re able to understand which --- and which means you will be able to predict …
Mien-Chie Hung, PhD:
Yeah.
T.A. Rosolowski, PhD:
Got you.
Mien-Chie Hung, PhD:
And then, one can design clinical trial, too. One can design clinical trial, too. You --- you go to this end ____mTor, you have a series serious marker you can follow. One new principle can use combination therapy. So that’s why we ___ … that. You know, in the lab, you are not --- I’m not doing work with patients but from the clinical observation and then from our study we can even pro --- and they --- they may not even happen yet but we are already prov --- end up, yeah. But the time when we discover this one, then I called _____ 1:09:59 hold --- hold a minute, wait a minute, pancreatic cancer doesn’t work. Ovarian cancer doesn’t work. And brain tumor doesn’t work, right? But only basal cell carcinoma works. And they approve it, right? But, you know why? Basal cell car --- carcinoma was activated only by this pathway.
T.A. Rosolowski, PhD:
Wow.
Mien-Chie Hung, PhD:
But pancreatic cancer, ovarian cancer, and now we know, breast cancer, the same, too. Now mTor pathway was activated. And that’s why clinical trial doesn’t work. Because they targeted the same molecule. You can go this way, you can go this way. You block this one, but this cancer cell, this pathway so --- and now we provide an option. Now I’m talking to several clinicians here, tryomg to see where we can design clinical trial to test that. And in a way, I’m not developing a drug. But I’m identifying a marker to guide it. Say what patient population will respond to what. And then, let them be treated this way. And that’s what we can contribute in, my friend. 20 years ago, we could not do that. For HER2 overexpression at that time, the HER2 ___ HER2, HER2, HER2, HER2, HER2. At that time, there is no signal pathway, but now, there are 300 signal pathways. And so we’re doing a lot of this kind of stuff. And again --- and this is the most recent data, right? And you ___ 1:11:13 because by the time when your book came out, some of the stuff we predict ___ magic going to happen.
T.A. Rosolowski, PhD:
Right.
Mien-Chie Hung, PhD:
And then in the future, when people read it, hey, at the time when we talk about it and five years later, …
T.A. Rosolowski, PhD:
It was there.
Mien-Chie Hung, PhD:
Another one, for example, recently we have --- this a triple negative. Let --- let’s take another one. The --- the HER2 --- EGF receptor, you know the …
T.A. Rosolowski, PhD:
The HER2 …which receptor?
Mien-Chie Hung, PhD:
Okay. HER2 is one receptor. There’s his brother, EGF receptor. You know Cetuximab right? You know John Mendelsohn’s drug? Right? John Mendelsohn’s drug, right, is a monoclonal antibody EGF receptor. And HER2 and EGF receptor are brothers, okay? Okay. But that drug has been approved. But you know that story, right?
T.A. Rosolowski, PhD:
Tell it.
Mien-Chie Hung, PhD:
No, no, no. When Mendelsohn____ we said with Inclone and then ______ that famous one, they are now in jail because their staff, they released the clinical trial --staff because 10 years ago, there was one big news. _____ Anyway, that’s not important. This stuff is important. The drug developed by John Mendelsohn called Cetuximab. You know that, right? That drug has been approved by FDA for colon cancer, and head and neck cancer. But that drug treated pancreatic cancer and breast cancer because … sounds familiar now? We talk about carcinoma --- carcinoma. This drug treated --- treated with the skin cancer work. Treats pancreatic cancer. Other cancers, it doesn’t work. Right? It’s because of signal cross talk.
T.A. Rosolowski, PhD:
Right.
Mien-Chie Hung, PhD:
Now, the EGF receptor overexpression in colon cancer --FDA approved, in head and neck cancer. ____ in the neck. It’s approved.
T.A. Rosolowski, PhD:
Approved, right.
Mien-Chie Hung, PhD:
But they did a clinical trial. They wanted it. This is targeted therapy --this EGF receptor. So if a cancer cell has EGF receptor overexpression, it should work. so So pancreatic cancer, breast cancer, they all have EGF receptor overexpression, but the clinical trial failed. So what does that tell us? It’s just like the --- the skin cancer. The skin cancer example is --- that means there’s something else…
T.A. Rosolowski, PhD:
There’s something else going on.
Mien-Chie Hung, PhD:
… making it --- it --- they should work, but it’s something else you have to take care of. And there are many, many people studying this one, and right now, there’s no clear cut conclusion there. I have something which are under review right now. We --- it probably doesn’t matter anyway. So this --- we actually --- because by the time your stuff come out, it’s probably ….
T.A. Rosolowski, PhD:
Been discovered.
Mien-Chie Hung, PhD:
… probably half year later, right? Okay. So we now discover the mechanism by which this receptor can be modified. And after modification, our data now show it’s become resistant to Cetuximab. So when I say modification, I mean, --remember I told you receptor has one --- one half outside, one half inside, right? And then when you use the Cetuximab, the monoclonal body to do therapy. This monoclonal body comes on the block --- you inject into block. And the cancer cell is here. Then this --- this cancer cell can
T.A. Rosolowski, PhD:
___ inside, outside receptor? Yeah.
Mien-Chie Hung, PhD:
Yeah. And then monoclonal body cancels this one, okay? And then you cancel it, then you degrade this one, so, you can kill cancer cells. Now what we found was this guy can be modified. And there are some specific amino acids that can modify it. After modification, this becomes --- cannot find. And therefore, this cancer cell, if it had this modification, this drug doesn’t work. And for cancer cell to work, this --- this drug had to come to find and kill it. But now, we found --- there’s some modification here. And that modification make it difficult for this guy to find. So they’ll --- that cancer cell resistant. And we are testing right now that is it. If that the case, we can identify this one.
T.A. Rosolowski, PhD:
And you want to do that.
Mien-Chie Hung, PhD:
Yeah, we know it, right? so So we say, hey, if this patient --- this modified, don’t do this drug, it’s not going to work. And then, we know --- we now know triple-negative breast cancer, one type of breast cancer, 50% have this. So my prediction is my prediction ___. If we remove this 50% and take those clinical trial data, if the clinical trial fails, failure doesn’t mean all patients have no response. Some patients, a very small number of patients respond. So if the response rate is too late --- too low, the FDA is not going to approve it, right? But if we know who are not responding, that’s a ____ way. So if you look at that data, it maybe approvable. And then if that is the case, then we can initiate another trial.
T.A. Rosolowski, PhD:
Right.
Mien-Chie Hung, PhD:
And just on purpose, you exclude those patient because it not going to work. It not going benefit you. But for those patients who are EFG receptor positive but there’s no mo --- modification, so we know it’s going to respond, then we may be able to make this --- again, I don’t want to develop a drug. Maybe it will help a patient in such a way that this --- let’s say breast cancer --- certainly portion of population with breast cancer is supposed to respond to this drug, but the FDA didn’t approve it. But we don’t have a way to identify who’s going to respond. So, the drug is not available for ____. We’re stuck. But if now we can tell them, say, hey, this population, with this --- we know how detect it, right? You are going to respond. And you’re not going to respond --- if you’re not going to respond, don’t do it. And then, take this responding one to the clinical trial. And then improve the --- the responding rate. We may be able to help the company to get FDA to approve this drug for breast cancer. And the long-term goal is, the
Recommended Citation
Hung, Mien-Chie PhD and Rosolowski, Tacey A. PhD, "Chapter 10: Research into Receptors, Pathways, Cross-Talk and the Utility of Existing Drugs" (2014). Interview Chapters. 1162.
https://openworks.mdanderson.org/mchv_interviewchapters/1162
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